Cytokines produced by islet-infiltrating mononuclear leukocytes may be involved in islet beta-cell destruction and IDDM. To determine which cytokine(s) might be involved in islet beta-cell destruction, we used a reverse transcriptase-polymerase chain reaction assay to compare levels of cytokine mRNA expression in mononuclear leukocytes freshly isolated from islets of four groups of BB rats aged 60-75 days: diabetes-prone (DP) rats, DP rats protected from diabetes by injection of complete Freund's adjuvant (CFA) at age 25 days, acutely diabetic rats, and diabetes-resistant (DR) rats. We found that islet mononuclear leukocyte levels of gamma-interferon (IFN-gamma) mRNA were significantly higher in DP and diabetic rats than in DR rats, whereas CFA-treated DP rats had similar IFN-gamma mRNA levels to DR rats. Also, interleukin (IL)-2 mRNA levels tended to be higher in islet leukocytes from DP and diabetic rats than from DR rats. Tumor necrosis factor-alpha, IL-4, and IL-10 mRNA levels were not significantly different in islet leukocytes from the four groups of rats. These findings suggest that production of T-helper 1 (Th1)-type cytokines, IFN-gamma and IL-2, by islet-infiltrating cells in BB rats is associated with beta-cell destruction and IDDM development.

No abstract

The pathogenetic role of interferon‐γ (IFN‐γ) in acute graft‐versus‐host disease (GVHD) was examined in a murine model. IFN‐γ gene expression was evaluated by northern blotting and mRNA in situ hybridization. The temporal and tissue specific patterns of IFN‐γ gene expression were related to the patterns of major histocompatibility complex (MHC) antigen induction and of tissue injury. Markedly increased levels of IFN‐γ transcripts were seen in the spleen during the early lymphoproliferative phase and coincided with widespread MHC induction in non‐lymphoid tissues. Increased IFN‐γ transcripts were also found in the non‐lymphoid target tissues during the phase of subsequent tissue injury. These findings support a role for IFN‐γ in leading to widespread MHC induction during acute GVHD and suggest that IFN‐γ may also contribute to target tissue injury during acute GVHD. Copyright © 1999 John Wiley & Sons, Ltd.

No abstract

No abstract